PROJECT SUMMARY Accidental falls among people aged 65 years and older cause approximately 2.7 million injuries, 27,000 deaths, and cost more than 34 billion dollars in the US annually. The risk of an accidental fall is substantially higher in the aging population compared to younger adults; one third of adults over 65 years of age fall annually and this increases to 50% over 80 years. Common causes of accidental falls in the older population include tripping, or slipping on wet or polished floors. Despite the prevalence of accidental falls in the aging population and disparity with younger adults, the effect of aging on how the musculoskeletal system adapts to challenging conditions, such as slippery ground, is poorly understood. While researchers have identified risk factors for falls including lower-extremity weakness, knee joint instability, environmental hazards and cognitive impairment, underlying mechanisms driving musculoskeletal adaptation are poorly understood. There is a gap in understanding of the mechanisms of musculoskeletal adaptation to challenging conditions, differences in musculoskeletal adaptation between young and older populations, and the relationship between knee joint instability and whole body musculoskeletal function (movement, muscle forces). The goals of this proposed foundational study are to 1) elucidate how young and older populations respond to challenging conditions, including environmental, physical and cognitive changes, 2) establish a functional measure of knee joint stability, and 3) quantify relationships between knee joint stability and whole-body musculoskeletal function. Our team will (1) develop a unique experimental dataset of whole-body kinematics, ground reaction forces, strength and balance testing, and bony anatomy, for cohorts of young and older adults performing routine daily activity under a variety of environmental, physical, and cognitive external conditions, (2) apply a combined experimental and computational approach to predict muscle force and joint stability, and (3) determine the strength of relationships between knee joint stability and whole-body musculoskeletal metrics typically associated with risk of falls (muscle strength, whole-body movement, balance). While the proposed foundational study focuses specifically on identifying musculoskeletal adaptations in response to challenging conditions and links to joint stability in young (low risk) and older (high risk) adults, we anticipate that successful completion of this work will lead to further studies to develop targeted muscle training programs that will improve joint stability and musculoskeletal function, and optimize surgical and therapeutic interventions, such as bracing and total knee arthroplasty, to establish joint-level stability which best facilitates whole-body function, mobility, and stability.